Clinical Outcomes of Proton Beam Therapy for Stage I Lung Cancer in Patients with Interstitial Pneumonia: A Multi-Institutional Retrospective Study in Japan

Abstract

Stereotactic body radiotherapy (SBRT) is a standard option for medically inoperable stage I non-small cell lung cancer (NSCLC). However, interstitial pneumonia (IP) is considered to be a relative contraindication for SBRT. The rates of Grade ≥3 pneumonitis after SBRT in patients with IP have been reported to range from 10% to 38%. Proton beam therapy (PBT) might have an advantage in treating patients with IP. The purpose of this study is to clarify the safety and the effectiveness of PBT for Stage I NSCLC in patients with IP. Six hundred sixty-nine patients with histologically or clinically diagnosed Stage I NSCLC according to the 7th edition of UICC received passive-scattering PBT from April 2004 and December 2013 at 8 institutions in Japan. Of them, 51 patients with comorbidity of IP, which was diagnosed by CT findings, were identified and retrospectively analyzed survivals, local control, and adverse events. Forty-six (90.2%) of 51 patients were male, with a median age of 75 years (range, 60–89 years). Ten (19.6%) patients required corticosteroids or immunosuppressants, and 4 (7.8%) patients received long-term oxygen therapy. NSCLC was histologically confirmed in 32 (62.7%) patients. Clinical T stages included T1a (n = 19; 37.2%), T1b (n = 14; 27.4%), and T2a (n = 18; 35.3%). The total irradiation doses of PBT ranged from 89.3 to 131.3 Gy (RBE) BED10 (median, 109.6 Gy (RBE)). The median follow-up period was 25.1 months (range, 3.1-65.9 months) for all patients. The 2-year overall survival, disease specific survival, progression-free survival, and local progression-free rates for all patients were 71.6% (95% confidence interval [CI]: 56.9–82.8%), 83.9% (95% CI: 69.7–92.1%), 52.2% (95% CI: 38.2–65.9%), and 82.0% (95% CI: 66.5–91.2%), respectively. The incidence of Grade 2, 3, 4, and 5 pneumonitis including exacerbation of IP was 13.7%, 0%, 0%, and 3.9%, respectively. The incidence of Grade 3 dermatitis was 2.0%. No Grade 4 or severe adverse events, other than pneumonitis, were observed. PBT for Stage I NSCLC in patients with IP seems to be tolerable and effective.